IL-33 aggravates extranodal NK/T cell lymphoma aggressiveness and angiogenesis by activating the Wnt/ß-catenin signaling pathway.

Extranodal NK/T cell lymphoma (ENKTCL) is an extremely aggressive form of lymphoma and lacks of specific diagnostic markers. The study intended to unearth the role of interleukin-33 (IL-33) in ENKTCL. RT-qPCR was conducted to assess mRNA levels of ENKTCL tissues and cells, while western blot assay was performed for evaluating protein levels. Plate cloning experiment and transwell assay were employed to measure aggressiveness of ENKTCL. Tube formation assay was executed to determine the angiogenesis ability. Mice ENKTCL xenograft model was designed to probe the impacts of IL-33 in vivo. IL-33 and suppression of tumorigenicity 2 receptor (ST2, receptor of IL-33) were enhanced in ENKTCL. IL-33 inhibition suppressed viability, migration, and invasion of ENKTCL cells. Moreover, IL-33 knockdown restricted angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, Wnt/ß-catenin pathway associated proteins (ß-catenin, c-myc, and cyclin D1) were downregulated by loss of IL-33. However, these impacts were overturned by Wnt/ß-catenin signaling agonist lithium chloride (LiCl). Additionally, IL-33 silencing exerted anti-tumor effect via Wnt/ß-catenin pathway in vivo. Silencing of IL-33 inhibited ENKTCL tumorigenesis and angiogenesis by inactivating Wnt/ß-catenin signaling pathway. As such, IL-33 might be a prospective treatment target for ENKTCL.

[Establishment of an Engineered Bacterial Membrane Biomimetic Nanodrug Delivery System and Its Role in the Treatment of Glioma]. / å·¥ç¨‹åŒ–ç»†èŒè†œä»¿ç”Ÿçº³ç±³è¯ç‰©é€’é€ç³»ç»Ÿçš„å»ºç«‹åŠåœ¨è„‘èƒ¶è´¨ç˜¤æ²»ç–—ä¸­çš„ä½œç”¨ç ”ç©¶.

Objective: To develop engineered bacterial membrane biomimetic nanoparticles, Angiopep-2 E. coli membrane (ANG-2 EM)@PDA-PEI-CpG (ANG-2 EM@PPC), for efficient targeted drug delivery in the treatment of glioma, and to provide theoretical and technical support for targeted glioma therapy. Methods: The expression of inaX-N-angiopep-2 engineered bacteria was constructed in the laboratory, and ANG-2 EM was obtained through lysozyme treatment and ultrafiltration centrifugation. ANG-2 EM@PPC was prepared by ultrasonication of bacterial membranes. Western blotting, agarose gel electrophoresis, and transmission electron microscopy (TEM) were used to verify the preparation. Particle size and Zeta potential were measured to investigate the stability of ANG-2 EM@PPC. Regarding cell experiments, CCK-8 assay was performed to determine the effect of ANG-2 EM@PPC on the survival rate of neutrophils. A flow chamber model was designed and constructed, and the uptake efficiency of neutrophils was measured by flow cytometry to investigate the hitchhiking efficiency of ANG 2 EM@PPC on neutrophils in inflammatory environment. Neutrophil death patterns were characterized by fluorescence microscopy, and flow cytometry and Western blotting were performed to examine neutrophil apoptotic bodies and the proportion of apoptotic bodies produced. Regarding animal experiments, a mouse model of in situ glioma was established and the inflammatory environment of tumor tissue was verified. The tumor model mice were divided into three groups, including DiR group, EM@PPC group, and ANG-2 EM@PPC group (all n=3), which were injected with DiR, ANG-2 EM@PDA-PEI-CpG, and EM@PDA-PEI-CpG via the tail vein, respectively (all at 10 mg/kg). Fluorescence images of organs and the brain were used to examine the distribution of the three formulations in vivo and in the brain. The tumor model mice were further divided into PBS group, PDA group, PC group, PPC group, EM@PPC group, and ANG-2 EM@PPC group (all n=4), which were injected with PBS, PDA, PC, PPC, EM@PPC, and ANG-2 EM@PPC injected via the tail vein, respectively (all at 10 mg/kg). Imaging was performed in vivo to observe tumor regression, and the survival rate and body mass of mice were measured to evaluate in vivo pharmacodynamics. TUNEL staining (brain tissue) and HE staining (brain, heart, liver, spleen, lung and kidney tissues) were performed to evaluate the therapeutic effect. Results: The results of TEM showed successful preparation of engineered bacterial membrane biomimetic nanoparticles, with PPC exhibiting a distinct shell-core structure and a shell thickness of about 8.2 nm. Due to the coating of ANG-2 EM, the shell thickness of ANG-2 EM@PPC increased to about 9.6 nm, with a clear bacterial membrane layer on the surface. Stability was maintained for at least one week. ANG-2 EM@PPC had no significant effect on the activity of neutrophils according to the findings from the CCK-8 assay. Flow cytometry showed that ANG-2 EM@PPC uptake is enhanced in activated neutrophils and hitchhiking on neutrophils was more efficient in the stationary state than that in the flowing condition. Compared with the EM@PPC group, the neutrophil hitchhiking ability of the ANG-2 EM@PPC group was enhanced (uptake efficiency 24.9% vs. 31.1%). Fluorescence microscopy showed that ANG-2 EM@PPC changed the death pathway of neutrophils from neutrophil extracellular traps-osis (NETosis) to apoptosis. Western blot confirmed the production of neutrophil apoptotic bodies, and flow cytometry showed that the production rate was as high as 77.7%. Animal experiments showed that there was no significant difference in the distribution of engineered bacterial membrane biomimetic nanoparticles in the organs (heart, liver, spleen, lungs, and kidney) in the DiR group, the EM@PPC gropu, and the ANG-2 EM@PPC group (P>0.05), but there was higher distribution in the brain tissue in EM@PPC and ANG-2 EM@PPC groups compared to the DiR group (P<0.05). Engineered bacterial membrane biomimetic nanoparticles crossed the blood-brain barrier (BBB), and exhibited high affinity to and internalization by neutrophils located in brain tumors. Compared with PBS, PDA, PC, and PPC groups, the survival rate and body mass of mice in the EM@PPC group were improved, tumor fluorescence intensity was weakened, and apoptotic cells were increased. These trends were even more prominent in the ANG-2 EM@PPC group. No abnormality was found in the HE staining of any group. Conclusion: An ANG-2 EM@PPC nanodelivery system with inflammation response characteristics was successfully prepared, capable of crossing BBB and targeting the tumor inflammatory microenvironment to improve the anti-glioma efficacy. This study provides a new drug delivery strategy for glioma treatment and offers a new idea for targeted drug delivery in the non-invasive inflammatory microenvironments in other central nervous system diseases.

Liquid Crystals under Confinement in Submicrometer Capsules.

Liquid crystal (LC) ordering and phase transition behavior under confined conditions have attracted extensive attention and enabled many applications. However, the ordering and phase transition behavior of LCs in submicrometer capsules have seldom been studied, primarily due to the lack of proper capsulizing and visualization approaches to such small LC microcapsules. Herein, we achieve submicrometer LC capsules with the sizes down to 100 nm by using emulsion-based interfacial sol-gel reaction. The behavior of LCs under the submicrometer confinement conditions is investigated while the sizes and chemical composition of the microcapsule shell surface are tuned in a controllable way. The phase transition temperatures of LCs in the submicrometer capsules shift from those of bulk LCs due to the surface-induced ordering of LCs under the strong confinement conditions, which causes formation of topological defects and alters the order parameter. Using nonlinear optical imaging technology, we explore the structures of director field of LCs that arise as a result of the competition between the surface boundary conditions and LC elasticity. The results show that the nanoscale encapsulation can significantly influence the structural configurations of the director and phase transitions of LCs under various confinement conditions.

Monochromatic visible light "photoinitibitor": Janus-faced initiation and inhibition for storage of colored 3D images.

Controlling the kinetics and gelation of photopolymerization is a significant challenge in the fabrication of complex three-dimensional (3D) objects as is critical in numerous imaging, lithography, and additive manufacturing techniques. We propose a novel, visible light sensitive "photoinitibitor" which simultaneously generates two distinct radicals, each with their own unique purpose-one radical each for initiation and inhibition. The Janus-faced functions of this photoinitibitor delay gelation and dramatically amplify the gelation time difference between the constructive and destructive interference regions of the exposed holographic pattern. This approach enhances the photopolymerization induced phase separation of liquid crystal/acrylate resins and the formation of fine holographic polymer dispersed liquid crystal (HPDLC) gratings. Moreover, we construct colored 3D holographic images that are visually recognizable to the naked eye under white light.

Orthogonal Reconstruction of Upconversion and Holographic Images for Anticounterfeiting Based on Energy Transfer.

Crosstalk-free reconstruction of multiple images within a single element can greatly boost the image capacity and information security. We herein demonstrate a viable approach by integrating upconversion and holographic images into a single holographic polymer nanocomposite. The holographic image is reconstructed through photopolymerization-induced phase separation under a 460 nm laser and identifiable under room light, while the upconversion image recognizable under a 980 nm laser is photopatterned via spatially photobleaching of the dye embedded in the upconversion nanoparticle (UCNP) shell under 365 nm light. To this end, the lanthanide-doped UCNP in the core/shell/shell nanostructure of NaYF4:20%Yb3+,0.5%Tm3+@NaYF4@SiO2 is designed, and the dye, fluorescein isothiocyanate (FITC), is fixed in the outermost SiO2 shell via the amine-isothiocyanate reaction and the subsequent sol-gel reaction. Energy transfer from the core of the UCNP to FITC embedded in the shell is critical to boosting the contrast of the upconversion image, which dials the emission color from blue to yellow-green. It is also found that the upconversion image can be brightened by increasing the UCNP content while the holographic image is weakened when the UCNP content is over 15 wt %. This study paves a new way toward advanced anticounterfeiting.

Highly Luminescent Liquid Crystals in Aggregation Based on Platinum(II) Complexes.

Luminescent liquid crystals (LLCs) attract considerable attention because of their broad applications in displays, chemosensors, and anti-counterfeiting. However, it remains challenging to achieve a high luminescence efficiency in LCs because of the common aggregation-caused quenching effect. Herein, we demonstrate a facile approach to designing LLCs with a high quantum yield up to 88% by deliberately tuning the aggregation behavior of platinum(II) complexes with alkoxy chains (CnH2n+1O-). LLCs in hexagonal columnar and rectangular columnar phases are achieved when n = 12 and 16, respectively, as revealed by one-dimensional wide-angle X-ray diffraction and small-angle X-ray scattering. These LLCs are able to not only exhibit strong emission at elevated temperatures but also show attractive reversible vapochromism upon alternative CH2Cl2 and EtOH fuming, which imparts added functions and promises technological utility.

One-Step and Metal-Free Synthesis of Triblock Quaterpolymers by Concurrent and Switchable Polymerization.

A one-step and metal-free route to triblock quaterpolymers from mixtures of vinyl monomers, epoxides, anhydrides, and racemic lactide (rac-LA) has been described, which bridges three polymerization cycles involving ring-opening copolymerization (ROCOP) of epoxides/anhydrides, ring-opening polymerization (ROP) of rac-LA, and RAFT polymerization of vinyl monomers. Taking advantage of the switchable polymerization between ROCOP and ROP, concurrent chain propagation of ROCOP/RAFT and ROP/RAFT sequentially occurs by using a trithiocarbonate compound with carboxylic group (TTC-COOH) as a versatile chain transfer agent. The multiple-chain transfer effect enables independent and precise control over the molecular weights of the three blocks and ensures narrow distribution of the resultant triblock quaterpolymers (D < 1.20). This work demonstrates the possibility to acquire block copolymers with high degree of structural complexities in a single efficient process by combining different block polymerization strategies.

Monochromatic "Photoinitibitor"-Mediated Holographic Photopolymer Electrolytes for Lithium-Ion Batteries.

A new polymer electrolyte based on holographic photopolymer is designed and fabricated. Ethylene carbonate (EC) and propylene carbonate (PC) are introduced as the photoinert substances. Upon laser-interference-pattern illumination, photopolymerization occurs within the constructive regions which subsequently results in a phase separation between the photogenerated polymer and unreacted EC-PC, affording holographic photopolymer electrolytes (HPEs) with a pitch of ≈740 nm. Interestingly, both diffraction efficiency and ionic conductivity increase with an augmentation of the EC-PC content. With 50 wt% of EC-PC, the diffraction efficiency and ionic conductivity are ≈60% and 2.13 × 10-4 S cm-1 at 30 °C, respectively, which are 60 times and 5 orders of magnitude larger than the electrolyte without EC-PC. Notably, the HPEs afford better anisotropy and more stable electrochemical properties when incorporating N,N-dimethylacrylamide. The HPEs exhibit good toughness under bending, excellent optical transparency under ambient conditions, and astonishing capabilities of reconstructing colored images. The HPEs here open a door to design flexible and transparent electronics with good mechanical, electrical, and optical functions.

IL-13 Contributes to Drug Resistance of NK/T-Cell Lymphoma Cells by Regulating ABCC4.

BACKGROUND: Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL), represents a rare subtype of T-cell lymphomas with aggressive clinical behavior and is relatively resistant to chemotherapy. However, there is relatively poor understanding of molecular pathogenesis of multidrug resistance in ENKTL. Here, we aimed to explore the biological roles and potential mechanism of IL-13 and ABCC4 in multidrug resistance of NK/T-cell lymphoma. METHODS: ELISA analysis was used to determine the level of serum IL-13 and immunohistochemical analysis was applied to detect the ABCC4 expression level in patients with human NK/T-cell lymphoma. Western blot assay was employed to measure the expression of ABCC4 in cells. Lenti-sh-ABCC4 viruses were constructed to knock down ABCC4 in YTS cells. CCK-8 assay and flow cytometric analysis were performed to detect the effects of IL-13 and ABCC4 on cell proliferation and apoptosis. CCK-8 assay was conducted to detect the effect of IL-13 and ABCC4 on cell sensitivity to adriamycin (ADM) in YTS cells. RESULTS: Levels of serum IL-13 and ABCC4 expression were observed to be upregulated in patients with human NK/T-cell lymphoma. Moreover, ABCC4 protein expression was also increased in NK/T-cell lymphoma YTS cells compared to the normal NK cells. Interestingly, IL-13 promoted ABCC4 expression in YTS cells. IL-13 promoted proliferation and suppressed apoptosis of YTS cells and reversed the effects of ABCC4 knockdown on promotive proliferation and inhibitory apoptosis. In addition, IL-13 enhanced YTS cell chemotherapy resistance to ADM by promoting ABCC4 expression. CONCLUSION: Our findings concluded that IL-13 inhibited chemotherapy sensitivity of NK/T-cell lymphoma cells by regulating ABCC4, disrupting which may effectively improve the therapy protocols against resistant NK/T-cell lymphoma.

Photoinitiation and Inhibition under Monochromatic Green Light for Storage of Colored 3D Images in Holographic Polymer-Dispersed Liquid Crystals.

Holographic photopolymer composites have garnered a great deal of interest in recent decades, not only because of their advantageous light sensitivity but also due to their attractive capabilities of realizing high capacity three-dimensional (3D) data storage that is long-term stable within two-dimensional (2D) thin films. For achieving high performance holographic photopolymer composites, it is of critical importance to implement precisely spatiotemporal control over the photopolymerization kinetics and gelation during holographic recording. Though a monochromatic blue light photoinitibitor has been demonstrated to be useful for improving the holographic performance, it is impractical to be employed for constructing holograms under green light due to the severe restriction of the First Law of Photochemistry, while holography under green light is highly desirable considering the relatively low cost of laser source and high tolerance to ambient vibration for image reconstruction. Herein, we disclose the concurrent photoinitiation and inhibition functions of the rose bengal (RB)/N-phenylglycine (NPG) system upon green light illumination, which result in significant enhancement of the diffraction efficiency of holographic polymer-dispersed liquid crystal (HPDLC) gratings from zero up to 87.6 ± 1.3%, with an augmentation of the RB concentration from 0.06 × 10-3 to 9.41 × 10-3 mol L-1. Interestingly, no detectable variation of the ϕ1/2kp/kt1/2, which reflects the initiation efficiency and kinetic constants, is given when increasing the RB concentration. The radical inhibition by RBH• is believed to account for the greatly improved phase separation and enhanced diffraction efficiency, through shortening the weight-average polymer chain length and subsequently delaying the photopolymerization gelation. The reconstructed colored 3D images that are easily identifiable to the naked eye under white light demonstrate great potential to be applied for advanced anticounterfeiting.